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SYNTHETIC CELLS
FIZZA KHAN
MPHIL BIOTECHNOLOGY
UNIVERSITY OF AGRICULTURE, FAISALABAD
DEFINITION
 An artificial cell or minimal cell or synthetic cell is an engineered particle that mimics one or many
functions of a biological cell.
 The term does not refer to a specific physical entity, but rather to the idea that certain functions or
structures of biological cells can be replaced or supplemented with a synthetic entity.
 Artificial cells are biological or polymeric membranes which enclose biologically active materials.
 A "living" artificial cell has been defined as a completely synthetically made cell that can capture energy,
maintain ion gradients, contain macromolecules as well as store information and have the ability
to mutate.
EXAMPLES
NANOPARTICLES LIPOSOMES POLYMERSOMES MICROCAPSULE
SYNTHETIC BIOLOGY
 Synthetic biology is a multidisciplinary area of
research that seeks to create new biological
parts, devices, and systems, or to redesign
systems that are already found in nature.
 Due to more powerful genetic
engineering capabilities and decreased DNA
synthesis and sequencing costs, the field of
synthetic biology is rapidly growing
HISTORY
 The first artificial cells were developed by Thomas Chang at McGill University in the 1960s.
 These cells were micron-sized and contained cell, enzymes, hemoglobin, magnetic
materials, adsorbents and proteins.
 Later artificial cells have ranged from hundred-micrometer to nanometer dimensions and can carry
microorganisms, vaccines, genes, drugs, hormones and peptides.
 The first clinical use of artificial cells was in hemoperfusion by the encapsulation of activated charcoal.
 Artificial cells in biological cell encapsulation were first used in the clinic in 1994 for treatment in a
diabetic patient
 On December 29, 2011, chemists at Harvard University reported the creation of an artificial cell
membrane.
 By 2014, self-replicating, synthetic bacterial cells with cell walls and synthetic DNA had been produced.
 In September 2018, researchers at the University of California developed artificial cells that can kill
bacteria.
BOTTOM-UP APPROACH FOR CONSTRUCTING SYNTHETIC CELL
 The ultimate goal for many is to construct an artificial cell from scratch.
 Synthetic biologists use engineering principles to design and construct genetic circuits for programming
cells with novel functions.
 A bottom-up approach is commonly used to design and construct genetic circuits by piecing together
functional modules that are capable of reprogramming cells with novel behavior.
 While genetic circuits control cell operations through the tight regulation of gene expression, a diverse
array of environmental factors within the extracellular space also has a significant impact on cell
behavior.
Assembling
CELL ENCAPSULATION METHOD
 The most common method of preparation of artificial cells is through cell encapsulation.
 Cell microencapsulation technology involves immobilization of the cells within a polymeric semi-
permeable membrane that permits the bidirectional diffusion of molecules such as the influx of oxygen,
nutrients, growth factors etc. essential for cell metabolism and the outward diffusion of waste products
and therapeutic proteins.
 Encapsulated cells are typically achieved through the generation of controlled-size droplets from a liquid
cell suspension which are then rapidly solidified or gelated to provide added stability.
 A drawback of the technique is that encapsulating a cell decreases its viability and ability to proliferate
and differentiate.
TECHNIQUES USED FOR THE PREPARATION OF EMULSION
HIGH PRESSURE
HOMOGENIZATION
MICROFLUIDIZATION DROP METHOD EMULSION METHOD
MEMBRANES OF SYNTHETIC CELLS
THE MINIMAL CELL
 A minimal cell is one whose genome only encodes the minimal set of genes necessary for the cell to
survive.
 The German pathologist Rudolf Virchow brought forward the idea that not only does life arise from cells,
but every cell comes from another cell; "Omnis cellula e cellula".
 In 2010, a team succeeded in creating a replicating strain of Mycoplasma mycoides (Mycoplasma
laboratorium) using synthetically created DNA deemed to be the minimum requirement for life which
was inserted into a genomically empty bacterium.
 As of 2016, Mycoplasma genitalium is the only organism used as a starting point for engineering a
minimal cell.
 Reduced-genome Escherichia coli is considered more useful, and viable strains have been developed
with 15% of the genome removed.
SYNTHETIC BLOOD CELLS
 Synthetic red blood cells mimic natural ones, and have new abilities
 Nano sized oxygen carriers are used as a type of red blood cell substitutes, although they lack other
components of red blood cells.
 A biological red blood cell membrane including lipids and associated proteins can also be used to
encapsulate nanoparticles and increase residence time in vivo by bypassing macrophage uptake and
systemic clearance
 A leuko-polymersome is a polymersome engineered to have the adhesive properties of a leukocyte.
APPLICATIONS OF SYNTHETIC CELLS
DRUG RELEASE AND DELIVERY
 Artificial cells used for drug delivery differ from other artificial cells since their contents are intended to
diffuse out of the membrane, or be engulfed and digested by a host target cell.
 Often used are submicron, lipid membrane artificial cells that may be referred to as nanocapsules,
nanoparticles, polymersomes, or other variations of the term.
ENZYME THERAPY
 Enzyme therapy is being actively studied for genetic metabolic diseases where an enzyme is over-
expressed, under-expressed, defective, or not at all there.
 The first enzyme studied under artificial cell encapsulation was asparaginase for the treatment
of lymphosarcoma in mice.
 These initial findings led to further research in the use of artificial cells for enzyme delivery
in tyrosine dependent melanomas.
 Artificial cell enzyme therapy is also of interest for the activation of prodrugs such as ifosfamide in
certain cancers.
HEMOPERFUSION
 The first clinical use of artificial cells was
in hemoperfusion by the encapsulation of activated
charcoal.
 Activated charcoal has the capability of adsorbing many
large molecules and has for a long time been known for its
ability to remove toxic substances from the blood in
accidental poisoning or overdose.
 However, perfusion through direct charcoal administration
is toxic as it leads to embolisms and damage of blood cells
followed by removal by platelets.
 Artificial cells allow toxins to diffuse into the cell while
keeping the dangerous cargo within their ultrathin
membrane.
 Artificial cell hemoperfusion has been proposed as a less
costly and more efficient detoxifying option
than hemodialysis.
OTHER APPLICATIONS
 They can be used as
1. Biomimetic systems to study and understand properties of biological cells
2. To investigate the dynamics of cells with minimal interference from cellular complexity
3. To explore new possible applications in place of biological cells.
4. Artificial cells have been successful for transplanting a number of cells including islets of
Langerhans for diabetes treatment, parathyroid cells and adrenal cortex cells.
5. Shortage of organ donors make artificial cells key players in alternative therapies for liver failure.
6. The oral ingestion of live bacterial cell colonies has been proposed and is currently in therapy for the
modulation of intestinal microflora, prevention of diarrheal diseases, treatment of H. Pylori infections,
atopic inflammations, lactose intolerance and immune modulation, amongst others.
FUTURE OF SYNTHETIC CELLS AND BIOLOGY
 Healthcare: Reimagining Medicine
 Advanced Materials: Inspired by Nature, Improved by Synthetic Biology
 Expanding the Host Repertoire
 Developing a Universal Production System
 Move to Cell-Free Environments
ACHIEVEMENTS
HEALTH AND SAFETY ISSUES
 There are 3 main field which are on risk:
1. Biosafety hazards to workers and the public
2. Biosecurity hazards stemming from deliberate engineering of organisms to cause harm
3. Environmental hazards
ETHICS AND CONTROVERSIES
 One ethical question is whether or not it is acceptable to create new life forms, sometimes known as
"playing God".
 What happens if a synthetic organism accidentally escapes?
 What if an individual misuses synthetic biology and creates a harmful entity?
 What if a new creation is deserving of moral or legal status?
REFERENCES
 https://en.wikipedia.org/wiki/Artificial_cell#:~:text=An%20artificial%20cell%20or%20minimal,supplemented%20with%20a%20synthetic%20entity.
 https://www.sciencedirect.com/topics/medicine-and-dentistry/artificial-cell
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041164/
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222523/#:~:text=They%20can%20be%20used%20as,be%20defined%20in%20many%20ways.
 https://www.frontiersin.org/articles/10.3389/fbioe.2019.00175/full
 https://en.wikipedia.org/wiki/Synthetic_biology#Ethics
THANK YOU
khfizza5887@gmail.com

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Synthetic cells

  • 1. SYNTHETIC CELLS FIZZA KHAN MPHIL BIOTECHNOLOGY UNIVERSITY OF AGRICULTURE, FAISALABAD
  • 2. DEFINITION  An artificial cell or minimal cell or synthetic cell is an engineered particle that mimics one or many functions of a biological cell.  The term does not refer to a specific physical entity, but rather to the idea that certain functions or structures of biological cells can be replaced or supplemented with a synthetic entity.  Artificial cells are biological or polymeric membranes which enclose biologically active materials.  A "living" artificial cell has been defined as a completely synthetically made cell that can capture energy, maintain ion gradients, contain macromolecules as well as store information and have the ability to mutate.
  • 4. SYNTHETIC BIOLOGY  Synthetic biology is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.  Due to more powerful genetic engineering capabilities and decreased DNA synthesis and sequencing costs, the field of synthetic biology is rapidly growing
  • 5. HISTORY  The first artificial cells were developed by Thomas Chang at McGill University in the 1960s.  These cells were micron-sized and contained cell, enzymes, hemoglobin, magnetic materials, adsorbents and proteins.  Later artificial cells have ranged from hundred-micrometer to nanometer dimensions and can carry microorganisms, vaccines, genes, drugs, hormones and peptides.  The first clinical use of artificial cells was in hemoperfusion by the encapsulation of activated charcoal.  Artificial cells in biological cell encapsulation were first used in the clinic in 1994 for treatment in a diabetic patient  On December 29, 2011, chemists at Harvard University reported the creation of an artificial cell membrane.  By 2014, self-replicating, synthetic bacterial cells with cell walls and synthetic DNA had been produced.  In September 2018, researchers at the University of California developed artificial cells that can kill bacteria.
  • 6. BOTTOM-UP APPROACH FOR CONSTRUCTING SYNTHETIC CELL  The ultimate goal for many is to construct an artificial cell from scratch.  Synthetic biologists use engineering principles to design and construct genetic circuits for programming cells with novel functions.  A bottom-up approach is commonly used to design and construct genetic circuits by piecing together functional modules that are capable of reprogramming cells with novel behavior.  While genetic circuits control cell operations through the tight regulation of gene expression, a diverse array of environmental factors within the extracellular space also has a significant impact on cell behavior. Assembling
  • 7. CELL ENCAPSULATION METHOD  The most common method of preparation of artificial cells is through cell encapsulation.  Cell microencapsulation technology involves immobilization of the cells within a polymeric semi- permeable membrane that permits the bidirectional diffusion of molecules such as the influx of oxygen, nutrients, growth factors etc. essential for cell metabolism and the outward diffusion of waste products and therapeutic proteins.  Encapsulated cells are typically achieved through the generation of controlled-size droplets from a liquid cell suspension which are then rapidly solidified or gelated to provide added stability.  A drawback of the technique is that encapsulating a cell decreases its viability and ability to proliferate and differentiate.
  • 8. TECHNIQUES USED FOR THE PREPARATION OF EMULSION HIGH PRESSURE HOMOGENIZATION MICROFLUIDIZATION DROP METHOD EMULSION METHOD
  • 10. THE MINIMAL CELL  A minimal cell is one whose genome only encodes the minimal set of genes necessary for the cell to survive.  The German pathologist Rudolf Virchow brought forward the idea that not only does life arise from cells, but every cell comes from another cell; "Omnis cellula e cellula".  In 2010, a team succeeded in creating a replicating strain of Mycoplasma mycoides (Mycoplasma laboratorium) using synthetically created DNA deemed to be the minimum requirement for life which was inserted into a genomically empty bacterium.  As of 2016, Mycoplasma genitalium is the only organism used as a starting point for engineering a minimal cell.  Reduced-genome Escherichia coli is considered more useful, and viable strains have been developed with 15% of the genome removed.
  • 11. SYNTHETIC BLOOD CELLS  Synthetic red blood cells mimic natural ones, and have new abilities  Nano sized oxygen carriers are used as a type of red blood cell substitutes, although they lack other components of red blood cells.  A biological red blood cell membrane including lipids and associated proteins can also be used to encapsulate nanoparticles and increase residence time in vivo by bypassing macrophage uptake and systemic clearance  A leuko-polymersome is a polymersome engineered to have the adhesive properties of a leukocyte.
  • 13. DRUG RELEASE AND DELIVERY  Artificial cells used for drug delivery differ from other artificial cells since their contents are intended to diffuse out of the membrane, or be engulfed and digested by a host target cell.  Often used are submicron, lipid membrane artificial cells that may be referred to as nanocapsules, nanoparticles, polymersomes, or other variations of the term.
  • 14.
  • 15. ENZYME THERAPY  Enzyme therapy is being actively studied for genetic metabolic diseases where an enzyme is over- expressed, under-expressed, defective, or not at all there.  The first enzyme studied under artificial cell encapsulation was asparaginase for the treatment of lymphosarcoma in mice.  These initial findings led to further research in the use of artificial cells for enzyme delivery in tyrosine dependent melanomas.  Artificial cell enzyme therapy is also of interest for the activation of prodrugs such as ifosfamide in certain cancers.
  • 16. HEMOPERFUSION  The first clinical use of artificial cells was in hemoperfusion by the encapsulation of activated charcoal.  Activated charcoal has the capability of adsorbing many large molecules and has for a long time been known for its ability to remove toxic substances from the blood in accidental poisoning or overdose.  However, perfusion through direct charcoal administration is toxic as it leads to embolisms and damage of blood cells followed by removal by platelets.  Artificial cells allow toxins to diffuse into the cell while keeping the dangerous cargo within their ultrathin membrane.  Artificial cell hemoperfusion has been proposed as a less costly and more efficient detoxifying option than hemodialysis.
  • 17. OTHER APPLICATIONS  They can be used as 1. Biomimetic systems to study and understand properties of biological cells 2. To investigate the dynamics of cells with minimal interference from cellular complexity 3. To explore new possible applications in place of biological cells. 4. Artificial cells have been successful for transplanting a number of cells including islets of Langerhans for diabetes treatment, parathyroid cells and adrenal cortex cells. 5. Shortage of organ donors make artificial cells key players in alternative therapies for liver failure. 6. The oral ingestion of live bacterial cell colonies has been proposed and is currently in therapy for the modulation of intestinal microflora, prevention of diarrheal diseases, treatment of H. Pylori infections, atopic inflammations, lactose intolerance and immune modulation, amongst others.
  • 18. FUTURE OF SYNTHETIC CELLS AND BIOLOGY  Healthcare: Reimagining Medicine  Advanced Materials: Inspired by Nature, Improved by Synthetic Biology  Expanding the Host Repertoire  Developing a Universal Production System  Move to Cell-Free Environments
  • 20. HEALTH AND SAFETY ISSUES  There are 3 main field which are on risk: 1. Biosafety hazards to workers and the public 2. Biosecurity hazards stemming from deliberate engineering of organisms to cause harm 3. Environmental hazards
  • 21. ETHICS AND CONTROVERSIES  One ethical question is whether or not it is acceptable to create new life forms, sometimes known as "playing God".  What happens if a synthetic organism accidentally escapes?  What if an individual misuses synthetic biology and creates a harmful entity?  What if a new creation is deserving of moral or legal status?
  • 22. REFERENCES  https://en.wikipedia.org/wiki/Artificial_cell#:~:text=An%20artificial%20cell%20or%20minimal,supplemented%20with%20a%20synthetic%20entity.  https://www.sciencedirect.com/topics/medicine-and-dentistry/artificial-cell  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041164/  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222523/#:~:text=They%20can%20be%20used%20as,be%20defined%20in%20many%20ways.  https://www.frontiersin.org/articles/10.3389/fbioe.2019.00175/full  https://en.wikipedia.org/wiki/Synthetic_biology#Ethics